Lactobacillus Suppresses Tumorigenesis of Oropharyngeal Cancer via Enhancing Anti-Tumor Immune Response
Deficiency in T cell-mediated adaptive immunity, such as low CD8 T cell infiltration, inhibits the immune surveillance, promotes malignant transformation, and facilitates tumor growth. Microbiota dysbiosis diminishes the immune system and contributes to the occurrence of cancer. However, the impact...
Saved in:
Published in | Frontiers in cell and developmental biology Vol. 10; p. 842153 |
---|---|
Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
01.03.2022
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Deficiency in T cell-mediated adaptive immunity, such as low CD8
T cell infiltration, inhibits the immune surveillance, promotes malignant transformation, and facilitates tumor growth. Microbiota dysbiosis diminishes the immune system and contributes to the occurrence of cancer. However, the impact of oral dysbiosis on the occurrence and molecular mechanisms of oropharyngeal cancer (OPC) remains largely unknown. In the current study, we used 4-nitroquinoline-1-oxide (4NQO) to mimic tobacco-related carcinogenesis to generate a murine OPC model and determine the role of microbiota changes in OPC tumorigenesis. Our results showed that the oral flora composition of mice was deregulated during the tumorigenesis of OPC. The abundance of
,
,
,
, and
was increased, whereas the dominant genus
was gradually decreased with disease progression. We further demonstrated that infiltration of CD8
T lymphocytes was markedly reduced due to the reduction of
Supplementation of
increased the infiltration of CD8
T cells, promoted the expression of IFN-
and granzyme B, and lessened the OPC progression. Analyzing the metabolites of the
, we demonstrated that
enhanced the anti-tumor immune response by producing acetate in OPC development. Administration of acetate to mice could increase the expression of IFN-
and IFN-
-inducible chemokines in tumor tissues by activating GPR43 to promote the infiltration of CD8
T lymphocytes and substantially delay the development of OPC. Together, our data suggest that dysbiosis of oral microbiota promotes the tumorigenesis of OPC through downregulation of cytotoxic T lymphocytes.
and its metabolite acetate improve the tumor microenvironment, which could be applied in the treatment of OPC. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Xu Dong Zhang, The University of Newcastle, Australia This article was submitted to Cell Death and Survival, a section of the journal Frontiers in Cell and Developmental Biology Reviewed by: Xiaoqi Liu, University of Kentucky, United States Yining Li, Zhejiang University, China |
ISSN: | 2296-634X 2296-634X |
DOI: | 10.3389/fcell.2022.842153 |